Hereditary Coproporphyria

Cpo Coproporphyrinogn Oxid Def

Hereditary coproporphyria (HC) is a rare disease originating from detrimental changes in the gene of the mitochondrial enzyme coproporphyrin-III oxidase (CPO). The enzyme malfunction results in pathologically high urine concentrations of porphobilinogen and 5-aminolevulinic acid. There is no cure for hereditary coproporphyria but a carbohydrate-rich diet, as well as general drug and alcohol abstinence, reduce the risk of acute porphyria attacks.

Hereditary coproporphyria is passed on in an autosomal dominant manner. It is caused by a set of mutations of the CPOX gene which drastically downregulates the enzymatic activity of CPO. CPO is involved in porphyrin and heme biosynthesis [1] [2].

In its chronic form, hereditary coproporphyria patients typically develop a long-lasting cutaneous photosensitivity in sun-exposed body parts such as hands and face. These body parts typically show a very fragile skin, hyperpigmented scars and bullae [3].

The probability of prevalence of the pathogenic CPOX mutations is equal in both, men and women. However, acute attacks affect women more often, in particular between menarche and menopause (age- 16 to 45). Attacks before puberty are very rare [3].

A case of hereditary coproporphyria was reported, he was a 21-year-old farmer, presenting with abdominalpain and fever.[ncbi.nlm.nih.gov]

A 23-year-old man with epilepsy and a past history of abdominalpain and ileus, developed hypertension and arm and bulbar weakness when valproic acid and carbamazepine were reinitiated.[ncbi.nlm.nih.gov]

Other symptoms included intermittent headache, fatigue, abdominalpain and nausea. Porphyrin studies were markedly raised, with features consistent with hereditary coproporphyria (HCP).[ncbi.nlm.nih.gov]

Both are considered rare differential diagnosis for acute abdominalpain. Case report 17 year old boy of Algerian origin presented with long history of recurrent episodes of fever, abdominalpain since infancy.[ped-rheum.biomedcentral.com]

Hereditary coproporphyria (HCP) is a rare inherited form of liver (hepatic) porphyria, characterized by neurological symptoms in the form of episodes (acute attacks) of stomach pain, nausea, vomiting, weakness, numbness, and pain in the hands and feet[rarediseases.info.nih.gov]

Other symptoms included intermittent headache, fatigue, abdominal pain and nausea. Porphyrin studies were markedly raised, with features consistent with hereditary coproporphyria (HCP).[ncbi.nlm.nih.gov]

However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use.[ncbi.nlm.nih.gov]

Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria.[ncbi.nlm.nih.gov]

Proper drug selection is most difficult when it comes to treatment of the seizures that can accompany HCP, as most anti-seizure medications can make the symptoms worse.[en.wikipedia.org]

A 9-year-old boy with mental deterioration and epilepsy suffered an acute attack of hereditary coproporphyria associated with worsening of seizure control.[ncbi.nlm.nih.gov]

Signs and symptoms present during the attacks may include body pain, nausea and vomiting, increased heart rate ( tachycardia ), and high blood pressure. [2] Less common symptoms include seizures, skin lesions, and paralysis of the arms and legs, body[rarediseases.info.nih.gov]

His manifestations were composed of all classical symptoms of acute hepatic porphyrias i.e. convulsions, psychosis, hypertension and respiratory failure as well as dark redurine with positive Watson-Schwartz test.[ncbi.nlm.nih.gov]

He subsequently developed dark redurine, with dipstick testing showing ketones only. He additionally described transient auditory and visual hallucinations. Urine porphobilinogen was increased, consistent with an acute attack of porphyria.[journals.lww.com]

Patients usually have blistering skin lesions, hypertrichosis, scarring, and redurine during infancy or childhood. Concurrent conditions that affect the liver may worsen the disease severity; this has been described in a toddler with hepatitis A.[clinicaladvisor.com]

This treatment is not effective in other por- phyrias [19]. 36.8 Hepatoerythropoietic Porphyria 36.8.1 Clinical Presentation This rare disease is clinically similar to congenital erythro- poietic porphyria and usually presents with redurine and blistering[123doc.org]

In the initial screening procedure, it is reasonable to probe 5-aminolevulinic acid and porphobilinogen urine levels, which are expected to be increased by at least a factor of three during attacks. Urine porphyrin concentrations are another viable cross-check. Importantly, urine porphyrin levels can reduce back to normal or remain mildly elevated between attacks [4] [5]. Slightly increased but constant urine coproporphyrin levels are nonspecific and thus insufficient to corroborate the diagnosis. Serum sodium concentration should be checked in patients during attacks, since hyponatremia a quite common symptom. It is hardly feasible and advisable to directly measure the enzymatic activity of CPO.

Hereditary coproporphyria diagnosis mainly relies on solid evidence of elevated concentrations of coproporphyrins in the feces after a positive initial screening. Fecal coproporphyrin III levels can be up to 200 times higher than normal in absolute terms [6]. A direct initial test of fecal coproporphyrin III levels without further backup tests lacks specificity and sensitivity. The ratio of fecal coproporphyrin III to coproporphyrin concentrations has been shown to be a suitable check to probe for hereditary coproporphyria in adults. A dominant contribution (60-95%) of the coproporphyrin III isomer in this ratio is characteristic of hereditary coproporphyria, while it is smaller than 50% in control groups [7] [8].

Abdominal pain symptoms in hereditary porphyria have been rationalized with elevated urine levels of the heme precursor molecule delta-aminolevulinic acid. Administration of hemin relieves pain symptoms during attacks because it inhibits the catalysis of delta-aminolevulinic acid by aminolevulinic acid synthase-1 [9].

Prognosis With early diagnosis and management, attacks from porphyria are rarely fatal. Acute attacks are more rare than in cases of acute intermittent porphryia and, if the triggering factors are eliminated, the disease is rarely progressive.[orpha.net]

Results of exhaustive investigation of etiological factors for hepatocellular carcinoma were negative. Results of microscopic histological analysis of the nontumorous liver were normal.[ncbi.nlm.nih.gov]

Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria.[ncbi.nlm.nih.gov]

After an extensive workup, the etiology of the liver failure was determined to be due to hereditary coprophorphyria (HCP).[ncbi.nlm.nih.gov]

Etiology Hereditary coproporphyria is caused by a deficiency of coproporphyrinogen oxidase (CPO, the sixth enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid[orpha.net]

Summary Epidemiology The prevalence in Europe is estimated at about 1/1,000,000. Clinical description The disease manifests after puberty and preferentially affects women.[orpha.net]

Our findings add substantially to knowledge of the molecular epidemiology of HCP, show that single copies of CPO mutations that are known or predicted to cause "homozygous" HCP or harderoporphyria can produce typical HCP in adults, and demonstrate that[ncbi.nlm.nih.gov]

[…] neurovisceral attacks always have elevations of porphobilinogen and ALA, researchers still are unclear about how this leads to the symptomatic disease because most patients with the genetic defect have excessive porphyrin secretion but no symptoms. [1] Epidemiology[emedicine.medscape.com]

In an oral stomatology practice, a group of patients having oral conditions with unknown pathophysiology and multiple systemic complaints were evaluated for porphyrin abnormalities. Blood enzymes, urine and stool porphyrin panels were usually run.[ncbi.nlm.nih.gov]

The pathophysiology of both neurologic and psychiatric symptoms is not fully understood.[ncbi.nlm.nih.gov]

Pathophysiology Coproporphyria is an autosomal dominant disease that results from defects in the enzyme coproporphyrinogen oxidase. This enzyme speeds the conversion of coproporphyrinogen to protoporphyrinogen.[emedicine.medscape.com]

Very frequent premenstrual attacks can be prevented by a gonadotropin-releasing hormone (GnRH) analogue administered with expert guidance. In selected cases, frequent noncyclic attacks can be prevented by once- or twice-weekly infusions of hemin.[porphyriafoundation.blogspot.com]

Treatment is based on preventing the symptoms. An acute attack requires hospitalization, medications, and treatment with heme therapy. [4] Last updated: 9/4/2019[rarediseases.info.nih.gov]

The identification of the genetic defect in HCP families is of crucial importance to detect the carrier status which allows counselling to prevent possible triggering factors, e.g. certain drugs, alcohol, or fasting.[ncbi.nlm.nih.gov]

Avoiding your triggers will help prevent bouts of symptoms. Remember that everyone with porphyria is different. Some people have milder symptoms than others. Treatments can help you feel better and prevent complications.[webmd.com]

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